Abstract
Based on our original pyrazine hit, CP-0809101, novel conformationally-restricted 5HT2c receptor agonists with 2-piperazin-azaindane scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the selectivity against 5HT2a and 5HT2b receptors with excellent 2c potency. Orally-active and selective compounds were identified with dose-responsive in vivo efficacy in our pre-clinical food intake model.
Copyright 2009 Elsevier Ltd. All rights reserved.
MeSH terms
-
Administration, Oral
-
Animals
-
Anti-Obesity Agents / chemical synthesis*
-
Anti-Obesity Agents / chemistry
-
Anti-Obesity Agents / pharmacology
-
Aza Compounds / chemical synthesis*
-
Aza Compounds / chemistry
-
Aza Compounds / pharmacology
-
Dogs
-
Drug Design
-
Haplorhini
-
Humans
-
Obesity / drug therapy
-
Rats
-
Receptor, Serotonin, 5-HT2C / metabolism
-
Serotonin 5-HT2 Receptor Agonists*
-
Serotonin Receptor Agonists / chemical synthesis*
-
Serotonin Receptor Agonists / chemistry
-
Serotonin Receptor Agonists / pharmacology
Substances
-
Anti-Obesity Agents
-
Aza Compounds
-
Receptor, Serotonin, 5-HT2C
-
Serotonin 5-HT2 Receptor Agonists
-
Serotonin Receptor Agonists